Stable therapeutic radionuclide compositions and methods for preparation thereof

Abstract

Stable therapeutic radionuclide compositions comprising, for example, 186Re, 188Re and 131I stably bound to a proteinaceous targeting moiety and suitable for human in vivo administration are disclosed. Stabilizing agents preferably comprise antioxidants and challenging agents, and combination of HSA with an antioxidant and/or challenging agent provides enhanced long term stability. Ascorbic acid is an especially preferred stabilizing agent, which provides stability of therapeutic radionuclide compositions at levels of at least about 90% for several hours up to several days.

We claim: 
     
       1. A stable purified therapeutic radionuclide preparation suitable for in vivo administration comprising a therapeutic radionuclide selected from the group consisting of  186  Re;  188  Re;  90  Y;  153  Sm;  105  Rh and mixtures thereof linked to a targeting agent, the therapeutic radionuclide preparation also comprising an effective amount of a stabilizing agent comprising ascorbic acid and human serum albumin, wherein the radiochemical purity of the therapeutic radionuclide preparation is maintained at a level of at least about 90% for at least about 4 hours. 
     
     
       2. A therapeutic radionuclide preparation according to claim 1, comprising at least about 1 mg/ml of stabilizing agent. 
     
     
       3. A therapeutic radionuclide preparation according to claim 1, comprising from about 50 to about 500 mg human serum albumin. 
     
     
       4. A therapeutic radionuclide preparation according to claim 2, wherein the proteinaceous targeting moiety comprises an antibody or an antibody fragment. 
     
     
       5. A therapeutic radionuclide preparation according to claim 1, additionally comprising a pharmaceutically acceptable carrier or diluent. 
     
     
       6. A method for therapeutic treatment of neoplastic diseases, comprising administering to a patient a therapeutically effective amount of the pharmaceutically acceptable preparation of claim 5. 
     
     
       7. A therapeutic radionuclide preparation according to claim 4, comprising from about 1 mg/ml to about 20 mg/ml ascorbic acid. 
     
     
       8. A therapeutic radionuclide preparation according to claim 4, wherein the therapeutic radionuclide is selected from the group consisting of  186  Re and  188  Re. 
     
     
       9. A therapeutic radionuclide preparation according to claim 8, wherein the therapeutic radionuclide is  186  Re and the preparation has a specific activity of about 4 μCi/μg targeting agent to about 8 μCi/μg targeting agent. 
     
     
       10. A therapeutic radionuclide preparation according to claim 4, wherein the therapeutic radionuclide is  90  Y. 
     
     
       11. A therapeutic radionuclide preparation according to claim 4, wherein the targeting agent is a proteinaceous moiety.